Role of Cyclooxygenase-2 in Liver Injury Induced by Severe Acute Pancreatitis_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LI Chunsheng ¹ , CAI Lei ¹ , WANG Yinping ¹ , YANG Rong ² , ZHANG Xu ³

1.Department of General Surgery, Nanhui Center Hospital, Nanhui Branch of Huashan Hospital, Shanghai Fudan University of Medicine, Shanghai 201300, China;;
2.Department of Pathology, Gansu Cancer Hospital, Lanzhou 730050, China;;
3.Institute of Pathology, College of Basic Medical Sciences of Lanzhou University, Lanzhou 730000, ChinaCorresponding Author: LI Chun-sheng, E-mail: lcs950919@163.com;

Corresponding author：

Keywords：

Cyclooxygenase-2; Severe acute pancreatitis; Liver injury; Immunohistochemistry

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Abstract Full text Figures/Tables Video References Cited by

Objective 　To investigate the expression of cyclooxygenase-2 (COX-2) in liver tissue of severe acute pancreatitis (SAP) rats.
Methods 　A rat model of SAP was induced by retrograde infusion of 3.5% sodium taurocholate into the biliary-pancreatic duct. Eighty rats were randomly divided into SAP group and control group. The levels of serum amylase (AMY), alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor (TNF) -α and ascites AMY were detected dynamically at 4 h, 8 h, 16 h and 24 h after operation. The pancreatic and liver injuries were observed by light microscope. The expression of COX-2 in liver tissue was measured by immunohistochemistry.
Results 　Compared with the control group, the levels of serum AMY, ALT, AST, TNF-α and ascites AMY increased significantly at the time point of 4 h, 8 h, 16 h and 24 h (P lt;0.05). These changes were paralleled with the histopathological changes of pancreatic and liver tissue. The expression positive rates of COX-2 at the different time in the SAP group were higer than those of the control group (P lt;0.05). There was a significantly positive correlation between the expression of COX-2 and ALT (rs=0.949, P=0.039), AST (rs=0.972, P=0.016) and serum AMY (rs=0.944, P=0.041), respectively.
Conclusion 　Overexpression of COX-2 may play an important role in liver injury during SAP.

Citation： LI Chunsheng,CAI Lei,WANG Yinping,YANG Rong,ZHANG Xu. Role of Cyclooxygenase-2 in Liver Injury Induced by Severe Acute Pancreatitis. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2010, 17(4): 343-347. doi: Copy

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6.	Isogai M, Yamaguchi A, Hori A, et al. Hepatic histopathological changes in biliary pancreatitis [J]. Am J Gastroenterol, 1995; 90(3): 449-454.
7.	Norman J. The role of cytokines in the pathogenesis of acute pancreatitis [J]. Am J Surg, 1998; 175(1): 76-83.
8.	Bhanot UK, Mller P. Mechanisms of parenchymal injury and signaling pathways in ectatic ducts of chronic pancreatitis: implications for pancreatic carcinogenesis [J]. Lab Invest, 2009; 89(5): 489-497.
9.	Toomey DP, Murphy JF, Conlon KC. COX-2, VEGF and tumour angiogenesis [J]. Surgeon, 2009; 7(3): 174-180.
10.	Chien MH, Ku CC, Johansson G, et al. Vascular endothelial growth factor-C (VEGF-C) promotes angiogenesis by induction of COX-2 in leukemic cells via the VEGF-R3/JNK/AP-1 pathway [J]. Carcinogenesis, 2009 Oct 13 [Epub ahead of print].
11.	Bastos-Pereira AL, Lugarini D, de Oliveira-Christoff A, et al. Celecoxib prevents tumor growth in an animal model by a COX-2 independent mechanism [J]. Cancer Chemother Pharmacol, 2010; 65(2): 267-276.
12.	Chen B, Su B, Chen S. A COX-2 inhibitor nimesulide analog selectively induces apoptosis in Her2 overexpressing breast cancer cells via cytochrome c dependent mechanisms [J]. Biochem Pharmacol, 2009; 77(12): 1787-1794.
13.	Menczer J, Schreiber L, Kravtsov V, et al. Cox-2 immunohistochemical expression in epithelial ovarian carcinoma and platin sensitivity [J]. Eur J Gynaecol Oncol, 2009; 30(5): 531-535.
14.	李斌, 李玉民, 李汛, 等. 环氧合酶-2 对脓毒症大鼠肝损伤的影响 [J]. 中国普外基础与临床杂志, 2008; 15(4): 266-270.
15.	张宁, 陶凯雄, 王国斌, 等. 环氧合酶-2及血管生成素-2在大肠癌中的表达及临床意义 [J]. 中国普外基础与临床杂志, 2006; 13(5): 564-567.

1. Aoki H, Ohnishi H, Hama K, et al. Cyclooxygenase-2 is required for activated pancreatic stellate cells to respond to proinflammatory cytokines [J]. Am J Physiol Cell Physiol, 2007 ; 292(1): C259-C268.
2. 　O’Brien G, Shields CJ, Winter DC, et al. Cyclooxygenase-2 plays a central role in the genesis of pancreatitis and associated lung injury [J]. Hepatobiliary Pancreat Dis Int, 2005; 4(1): 126-129.
3. 　Ethridge RT, Chung DH, Slogoff M, et al. Cyclooxygenase-2 gene disruption attenuates the severity of acute pancreatitis and pancreatitis-associated lung injury [J]. Gastroenterology, 2002; 123(4): 1311-1322.
4. 　Aho HJ, Koskensalo SM, Nevalainen TJ. Experimental pancreatitis in the rat. Sodium taurocholate-induced acute haemorrhagic pancreatitis [J]. Scand J Gastroenterol, 1980; 15(4): 411-416.
5. 　Andrzejewska A, Dugosz J, Kurasz S, et al. Ultrastructure of liver in acute experimental pancreatitis in dogs treated with prostacyclin [J]. Exp Pathol, 1987; 31(1): 25-31.
6. 　Isogai M, Yamaguchi A, Hori A, et al. Hepatic histopathological changes in biliary pancreatitis [J]. Am J Gastroenterol, 1995; 90(3): 449-454.
7. 　Norman J. The role of cytokines in the pathogenesis of acute pancreatitis [J]. Am J Surg, 1998; 175(1): 76-83.
8. 　Bhanot UK, Mller P. Mechanisms of parenchymal injury and signaling pathways in ectatic ducts of chronic pancreatitis: implications for pancreatic carcinogenesis [J]. Lab Invest, 2009; 89(5): 489-497.
9. 　Toomey DP, Murphy JF, Conlon KC. COX-2, VEGF and tumour angiogenesis [J]. Surgeon, 2009; 7(3): 174-180.
10. 　Chien MH, Ku CC, Johansson G, et al. Vascular endothelial growth factor-C (VEGF-C) promotes angiogenesis by induction of COX-2 in leukemic cells via the VEGF-R3/JNK/AP-1 pathway [J]. Carcinogenesis, 2009 Oct 13 [Epub ahead of print].
11. 　Bastos-Pereira AL, Lugarini D, de Oliveira-Christoff A, et al. Celecoxib prevents tumor growth in an animal model by a COX-2 independent mechanism [J]. Cancer Chemother Pharmacol, 2010; 65(2): 267-276.
12. 　Chen B, Su B, Chen S. A COX-2 inhibitor nimesulide analog selectively induces apoptosis in Her2 overexpressing breast cancer cells via cytochrome c dependent mechanisms [J]. Biochem Pharmacol, 2009; 77(12): 1787-1794.
13. 　Menczer J, Schreiber L, Kravtsov V, et al. Cox-2 immunohistochemical expression in epithelial ovarian carcinoma and platin sensitivity [J]. Eur J Gynaecol Oncol, 2009; 30(5): 531-535.
14. 　李斌, 李玉民, 李汛, 等. 环氧合酶-2 对脓毒症大鼠肝损伤的影响 [J]. 中国普外基础与临床杂志, 2008; 15(4): 266-270.
15. 　张宁, 陶凯雄, 王国斌, 等. 环氧合酶-2及血管生成素-2在大肠癌中的表达及临床意义 [J]. 中国普外基础与临床杂志, 2006; 13(5): 564-567.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Role of Cyclooxygenase-2 in Liver Injury Induced by Severe Acute Pancreatitis

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